The present invention relates to new erythromycin derivatives, their preparation process and their use as medicaments.
A subject of the invention is the compounds of formula (I): 
in which:
X represents a CH2or SO2 radical or an oxygen atom, Y represents a (CH2)mxe2x80x94(CHxe2x95x90CH)n(CH2)o radical, with m+n+oxe2x89xa68, n=0 or 1.
Ar represents an optionally substituted aryl radical,
W represents a hydrogen atom, or the remainder of a carbamate function 
in which Rxe2x80x3 represents an alkyl radical containing up to 8 carbon atoms or an optionally substituted aryl radical,
Z represents a hydrogen atom or the remainder of an acid, as well as their addition salts with acids.
Among the addition salts with acids, there can be can mentioned the salts formed with the following acids: acetic, propionic, trifluoroacetic, maleic, tartaric, methanesulphonic, benzenesulphonic, p-toluenesulphonic, and in particular stearic, ethylsuccinic or laurylsulphonic.
The aryl radical can be a phenyl or naphthyl radical.
The aryl radical can also be a substituted or non-substituted heterocyclic radical such as the thienyl, furyl, pyrolyl, thiazolyl, oxazolyl, imidazolyl, thiadiazolyl, pyrazolyl or isopyrazolyl radical, a pyridyl, pyrimidyl, pyridazinyl or pyrazinyl radical, or also an indolyl benzofurannyl, benzothiazyl or quinolinyl radical.
These aryl radicals can contain one or more groups chosen from the group constituted by hydroxyl radicals, halogen atoms, NO2 radicals Cxe2x89xa1N radicals, alkyl, alkenyl or alkynyl, O-alkyl, O-alkenyl or O-alkynyl, S-alkyl, S-alkenyl or S-alkynyl and N-alkyl, N-alkenyl or N-alkynyl radicals, containing up to 12 carbon atoms optionally substituted by one or more halogen atoms, the 
Ra and Rb, identical or different, representing a hydrogen atom or an alkyl radical containing up to 12 carbon atoms, the 
R3 representing an alkyl radical containing up to 12 carbon atoms, or an optionally substituted aryl or heteroaryl radical, the following radicals: carboxylic aryl, O-aryl or S-aryl or heterocyclic aryl, O-aryl or S-aryl with 5 or 6 members containing one or more heteroatoms, optionally substituted by one or more of the substituents mentioned hereafter.
As preferred heterocycle, there can be mentioned among others: 
and the heterocyclic radicals envisaged in the European Patent Applications 487411, 596802, 676409 and 680967. These preferred heterocyclic radicals can be substituted by one or more functional groups.
A more particular subject of the invention is the compounds of formula (I) in which Z represents a hydrogen atom, these in which W represents a hydrogen atom, those in which X represents a CH2 radical, those in which Y represents a (CH2)3, (CH2)4 or (CH2)5 radical.
Among the preferred compounds of the invention, there can be mentioned the compounds of formula (I), in which Ar represents a heterocyclic aryl radical, such as for example those in which Ar represents a 4-quinolinyl radical optionally mono- or polysubstituted on one and/or the other of the 2 quinoline rings, and quite particularly the compounds of formula (I) in which AR represents a non-substituted 4-quinolinyl radical, or also for example the compounds of formula (I), in which Ar represents an optionally substituted: 
Among the preferred compounds of the invention, there can naturally be mentioned the products whose preparation is given hereafter in the experimental part.
The products of general formula (I) have a very good antiobiotic activity of gram+ bacteria such as staphylococci, streptococci, pneumococci.
The compounds of the invention can therefore be used as medicaments in the treatment of infections caused by susceptible germs and in particular, in that of staphylococcal infections, such as staphylococcal septicemias, malignant staphylococcal infections of the face of skin, pyodermatitis, septic or suppurating sores, boils, anthrax, phlegmons, erysipelas and acne, staphylococcia such as acute primary or post-influenzal angina, bronchopneumonia, pulmonary suppuration, streptococcal infections such as acute anginas, otitis, sinusitis, scarlet fever, pneumococcal infections such as pneumonia, bronchitis; brucellosis, diphtheria, gonococcal infection.
The products of the present invention are also active against infections caused by germs such as Haemophilus influenzae, Rickettsies, Mycoplasma, pneumoniae, Chlamydia, Legionella, Ureaplasma, Toxoplasma or by germs of the Mycobacterium genus.
Therefore a subject of the present invention is, as medicaments and in particular antibiotic medicaments, the products of formula (I) as defined above, as well as their addition salts with pharmaceutically acceptable mineral or organic acids.
A more particular subject of the invention is, as medicaments and in particular antibiotic medicaments, the products of Examples 1 or 2 and their pharmaceutically acceptable salts.
A subject of the invention is also the pharmaceutical compositions containing at least one of the medicaments defined above as active ingredient.
These compositions can be administered by buccal, rectal, parenteral route or by local route as a topical application on the skin and mucous membranes, but the preferred administration route is the buccal route.
They can be solid or liquid and be presented in the pharmaceutical forms commonly used in human medicine, such as for example, plain or sugar-coated tablets, capsules, granules, suppositories, injectable preparations, ointments, creams, gels; they are prepared according to the usual methods. The active ingredient or ingredients can be incorporated with excipients usually employed in these pharmaceutical compositions, such as talc, gum arabic, lactose, starch, magnesium stearate, cocoa butter, aqueous or non-aqeuous vehicles, fatty substances of animal or vegetable origin, paraffin derivatives, glycols, various wetting, dispersing or emulsifying agents, preservatives.
These compositions can also be presented in the form of a powder intended to be dissolved extemporaneously in an appropriate vehicle, for example apyrogenic sterile water.
The dose administered is variable according to the illness treated, the patient in question, the administration route and the product considered. It can be, for example, comprised between 50 mg and 500 mg per day by oral route, for an adult for the product of Example 1 or Example 2.
A subject of the invention is also a preparation process, characterized in that a compound of formula (II): 
in which X, Y and Ar are as defined above, is subjected to the action of a cleavage agent of cladinose in order to obtain the corresponding compound of formula (IA): 
in which X, Y and Ar retain their previous meaning, which is subjected, if desired, to the action of an esterification agent or to the action of an agent capable of introducing the carbamate radical.
In a preferred implementation the cleavage of cladinose in position 3 is carried out using an acid.
The products of formula (II) used as starting products, are products which can be prepared according to the process described in the European Patent Application 076093 filed on Dec. 6, 1995 by the Company ROUSSEL UCLAF.
The products of formula (II) can be prepared according to a process characterized in that a compound of formula (III): 
in which Bn represents a benzyloxycarbonyl radical and Ac an acyl radical containing 2 to 20 carbon atoms, is subjected to the action of a compound of formula (IV):
R3NH2 xe2x80x83xe2x80x83(IV) 
in which R3 represents the Xxe2x80x94Yxe2x80x94Ar radical, X, Y and Ar being defined as previously in order to obtain the compound of formula (V): 
which is subjected, if desired, to the action of a cleavage agent of the ester function in position 2xe2x80x2 in order to obtain the corresponding 2xe2x80x2xe2x80x94OH compound, then if desired, the compound thus obtained is subjected to the action of a reducing agent in order to carry out the cleavage of the benzyloxy carbonyl group in position 4xe2x80x3 and to obtain the product of formula (II).
The compounds of formula (III) used as starting products are known products desired in the European Patent 0,248,279.
The amines of formula (IV) are known in a general way and can be prepared according to the processes described in J. Med. Chem. (1982) Vol. 25, p. 947 and subsequent or also Tetrahedron Letters Vol. 32 No. 14, p. 1699, 1702 (1991).
The cleavage of the acetate in position 2xe2x80x3 is carried out using methanol.
The cleavage of the benzyloxycarbonyl group in position 4xe2x80x3 is carried out by reduction, for example using hydrogen in the presence of a palladium catalyst.
The salification is carried out using an acid according to standard processes.
The following examples illustrate the invention without however limiting it.